tbuckley/cabot-search huggingface dataset:
Oncologist perceptions of health inequity.
Authors: Alexandrina Balanean, Yolaine Jeune-Smith, Cherrishe Brown-Bickerstaff, Bruce A. Feinberg
Journal: Journal of Clinical Oncology (2023)

e18656 Background: The Institute of Medicine has reported on policies and practices based on assumptions and misinformation as pervading the educational, clinical, and payer sectors of health care. In these settings, unconscious bias toward marginalized populations can negatively impact patients, providers, health systems, and research. As national focus on diversity, equity, and inclusion expands, we sought to measure oncologists’ perceptions of issues surrounding health inequity in the context of patient care. Methods: In 2022, we surveyed oncologists’ perceptions of patient diversity, health inequity and disparities, unconscious bias, and their impact. Recruitment was conducted within the Cardinal Health Oncology Provider Extended Network (800 US practices). Participation was voluntary and compensated at fair market value. Results: In total, 192 oncologists responded. Of those surveyed: 48% estimated 10%–25% of their patients were in disadvantaged neighborhoods; 40% estimated 10%–25% were Hispanic or non-White; 69% estimated 10%–50% had low health literacy; and 92% estimated &lt; 10% were of sexual/gender minority. 96% felt prepared to talk with underrepresented patients, 80% agreed that health inequities exist, and 49% agreed they are especially prevalent in oncology. The majority also agreed that health inequities cause differences in care, outcomes, and access to care (80%, 82%, and 70%, respectively). 43% thought unconscious bias adversely affects Hispanic/non-White patients, and 74% perceived health care disparities among these patients. Additionally, 73% thought they would benefit from more research/education, and 50% had educated their coworkers on these issues and provided patient resources. Conclusions: Most oncologists are aware of health inequities and their adverse impact on clinical outcomes; they desire more education and want to help underrepresented patients. Health inequity and disparity may be driven subliminally by lower-quality patient-provider communication (eg, decreased conversationality and less participatory decision-making). Efforts at filling this need in oncology should be prioritized. [Table: see text]
Chronic lymphocytic leukemia/small lymphocytic lymphoma nationwide analysis: Comparing sociodemographic and survival outcomes among Hispanics and non-Hispanics in the United States.
Authors: Esteban Toro-Vélez, Daniel Rosas, Carolina Velez-Mejia, Qianqian Liu, Joel Michalek, Adolfo Enrique Diaz Duque
Journal: Journal of Clinical Oncology (2023)

e19505 Background: In essence, chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) are the same , CLL being the most common leukemia in Western countries. (Blood PMID 29540348, CA Cancer J Clin PMID 35020204) Survival outcomes in CLL/SLL among Hispanics (HI) and Non-Hispanics (NH) have been controversial. (Cancer Causes Control PMID 34677741, Cold Spring Harb Mol Case Stud PMID 33593728) This analysis attempts to clarify if sociodemographic characteristics influence survival of HI diagnosed with CLL/SLL in the United States (US). Methods: Retrospective data analysis on CLL/SLL patients in the US reported to the Surveillance, Epidemiology, and End Results (SEER) 18 database from 2000-2018. Demographics, disease characteristics, and survival patterns were analyzed across ethnic groups, HI vs NH. Kaplan-Meier and Cox regression analyses were used to compare overall survival (OS). Multivariate analysis and propensity score matching was performed, adjusting for age, stage, and B-symptoms. Results: 98884 CLL/SLL patients were included, 5012 HI. Males predominated in both HI and NH. HI compared to NH, were diagnosed at a younger median age, 68 years vs 70 years, respectively [p&lt;0.001]. Majority of patients belonged to the age bracket of 60-80 years; favoring a younger age distribution in HI. Most patients were white, and NH had greater heterogeneity [p&lt;0.001]. Unknown stage at diagnosis followed by advance stage (III/IV) prevailed for both ethnicities [p=0.075]. B-symptoms were mostly unknown in both groups. The tendency was towards not receiving radiation as part of the treatment. Survival probability at 2, 5 and 10 years for HI (0.829, 0.677, and 0.474) was similar compared to NH (0.831, 0.664 and 0.437), respectively. The median survival time was 9.3 years for HI vs 8.5 years for NH, with a statistically significant difference in OS favoring HI [p=0.0045] On multivariate analysis, patients older than 80 years and between 60-80, had worse OS than those less than 60, with hazard ratio (HR) 7.5 [95% CI: 7 – 8.1] and 2.5 [95% CI: 2.4-2.7], respectively. Also, stage III and IV, had inferior OS than those at early stages, with HR 1.4 [95% CI: 1.1 – 1.6] and HR 1.2 [95% CI: 1 – 1.4], respectively. Conclusions: In this analysis, HI with CLL/SLL have a superior OS, which was noted to be statistically significant. Also, multivariate analysis showed correlation of better OS when CLL/SLL was identified at a younger age and early stages. Although demographic differences may be driving the survival effect in HI as they were noted to be younger; identification and better understanding of intrinsic disease characteristics, treatment patterns, and biological variables; may aid in the understanding on how these factors contribute and impact the survival advantage in this ethnic group.
Comparison of cfDNA content in different cancer types with different extraction methods.
Authors: Wenlong Zhang, Yanan Zhao, Jun Li, Dan Cong, Di Zhou, Yang Yang, Yuansong Bai, Tianhao Mu, Ming Liu, Yan Yin, Shifu Chen, Yuanyuan Liu
Journal: Journal of Clinical Oncology (2023)

e15026 Background: ctDNA liquid biopsy technology has been widely used in the whole course of cancer management, from early screening and early diagnosis of tumors to tumor monitoring and medication guidance. However, the performances of ctDNA as a biomarker in these scenarios are different among different cancer types. One possible reason is that different types of cancer release different amounts of ctDNA or cfDNA, therefore, we explored the cfDNA levels in different cancer types in this study. Methods: We collected 15913 peripheral blood samples from 14686 cancer patients with different clinicopathologies, 256 patients with pulmonary nodules, and 971 healthy people. We isolated their plasma and extracted the cfDNA using QIAamp Circulating Nucleic Acid Kit, Apostle MiniMax cfDNA Extraction Kit or HaploX magnetic bead method cfDNA extraction kit. We calculated the average concentration of cfDNA (ng/ml) for different groups. Results: The number of samples of cervical cancer, liver cancer, glioma, colon cancer, prostate cancer, nasopharyngeal carcinoma, gallbladder carcinoma, melanoma, cholangiocarcinoma, colorectal cancer, breast cancer, gastric cancer, endometrial carcinoma, lung cancer, urothelial carcinoma, rectal cancer, ovarian cancer, healthy people, and pulmonary nodule patients are 93, 469, 113, 277, 139, 76, 89, 132, 171, 4010, 407, 547, 68, 7750, 46, 203, 96, 971 and 256, respectively. The cfDNA level of corresponding groups are 88.07, 79.51, 75.57, 63.58, 61.37, 59.09, 57.59, 57.16, 42.67, 34.73, 31.75, 31.37, 31.33, 29.84, 28.72, 28.69, 23.83, 17.82 and 12.54 ng/ml, respectively. The main groups are shown in the table below. Conclusions: The cfDNA concentrations of healthy people or pulmonary nodule patients were significantly lower than that of tumor patients, and there were also significant differences between different types of cancer. What's interesting, the cfDNA concentrations of lung cancer patients, pulmonary nodule patients and healthy people were quite different. What’s more, there were differences between Colon cancer and Rectal cancer patients. So, the cfDNA concentration maybe a good dimention to be used in early cancer screening and tracing of tumor types. [Table: see text]
An electrochemical molecular assay for the detection of cancer-associated Thomsen-Friedenreich glycans.
Authors: Saimon Moraes Silva, Chathurika Abeyrathne, Miaosi Li, Luke Robert Cossins, Anushka Samudra, Wren Greene, Simon Moulton
Journal: Journal of Clinical Oncology (2023)

e15046 Background: Abnormal glycosylation is a fundamental characteristic in cancer cells, where expression of glycans such as Thomsen-Friedenreich (T), Tn, and sialyl-Tn (STn) are related to particular tumour patterns. T, Tn and STn antigens are unusually short and truncated O-glycans expressed on glycoproteins synthesized within cancer cells and not normally found in healthy tissue or circulating within the blood. The association between blood circulating T-glycans and cancer progression and poor prognosis is now well-known and highlights great potential as biomarkers for cancer screening, diagnosis, and surveillance of diseases during treatment and following remission. Despite this potential, there is currently no established molecular assay for detecting or quantifying these biomarkers in blood biopsy samples. Methods: Using a test strip format reminiscent of a blood glucose test, a new electrochemical molecular assay is introduced for the detection of short O-glycans directly in unprocessed bodily fluids. This assay is based on a self-assembling sensing interface consisting of two glycoproteins, recombinant human lubricin (LUB) and peanut agglutin (PNA). In this interface, the LUB functions as both an anti-fouling layer which mitigates electrode passivation in blood and as a crucial component in the biosensing mechanism for generating readable electrical signals in the presence of target glycans. The PNA, a plant-based lectin, presents high binding specificity towards the T glycoform and functions as the sensor recognition element which is bound to the LUB through T glycans naturally present in the highly glycosylated protein backbone. In this sensing interface, electrical signals are generated by engineering a redox reporter, methylene blue into the LUB/PNA interfacial complex, where the electrical signal is altered by the capture of target glycans by PNA and its impact on the molecular dynamics of the LUB/PNA interfacial complex. Results: Using this test strip, it is possible to detect short cancer-related glycans in concentrations as low as nanomolar directly in small volumes of unprocessed whole blood. These test strips likewise show comparable results to an ELISA test developed in parallel for the detection of short O-glycans. The tests carried out with retrospective blood plasma samples from patients presenting three different tumour types, including prostate (18 patients), colorectal (15 patients), and breast cancer (6 patients), and plasma samples from healthy donors (10 different donors) showed differentiation of response signals between healthy and diseased patients. Conclusions: These findings highlight the clinical potential of this new disposable test strip for the detection of tumour associated glycans, which can be incorporated into point-of-care devices, for cancer monitoring and perhaps one day in screening and diagnosis.
A phase 2 randomized, open-label, multicentre study of sintilimab and anlotinib in combination with gemcitabine plus cisplatin (GemCis) as first-line therapy in patients (pts) with advanced biliary tract cancer (BTC): SAGC.
Authors: Li Jingjing, Qi Xu, Xiaoqing Xu, Luo Cong, Jieer Ying
Journal: Journal of Clinical Oncology (2023)

4015 Background: BTC has a higher incidence in China rather than worldwide, with extremely poor prognosis, and the efficacy of standard first-line therapy is rather limited. TOPAZ-1 study suggested the immune check-point inhibitor plus chemotherapy as first line in advanced BTC significantly improved OS and PFS with manageable safety, but the median OS was just 12.8 months. SAGC is the first randomized controlled phase 2 trial to evaluate immune check-point inhibitor plus antiangiogenic targeted drug plus chemotherapy in advanced BTC as first-line treatment. Methods: Overall 80 advanced BTC were randomized 1:1 to receive sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) in combination with GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles, followed by sintilimab (200mg every 3 weeks [Q3W]) and anlotinib (10mg po qd, Days 1-14 Q3W) (SAGC group) or GemCis (Gem 1000 mg/m2 and Cis 25 mg/m2 on Days 1 and 8 Q3W) for up to 8 cycles until disease progression or unacceptable toxicity (GC group). The primary objective was to assess the progression-free survival (PFS). Secondary endpoints included, objective response rate (ORR), overall survival (OS) and safety. Next generation sequencing (NGS) was performed on pre-treatment available tumor tissue in 58 patients to screen dominant patients of the therapy. Results: At the time of the final data cutoff (Sep. 22,2022), median follow-up was 13.4 mo, and 65/80 pts (81.3%) had discontinued tx. The confirmed median PFS was 8.6 months for SAGC group vs. 6.2 months for GC group (HR 0·37, p &lt; 0.01) and ORR was 52.8% for SAGC group vs. 29.4% for GC group. Grade 3/4 treatment-related adverse events (TRAEs) occurred in 77.5% of pts receiving sintilimab plus anlotinib plus GemCis and 40% of pts receiving GemCis. The results from NGS suggested that patients with TMB-H and ARID1A-WT may benefit more from combination therapy. Conclusions: In pts with advanced BTC, sintilimab plus anlotinib plus GemCis significantly improved PFS and ORR vs GemCis with manageable safety, indicating sintilimab plus anlotinib plus GemCis may be a new first-line standard of care regimen. Clinical trial information: NCT04300959 .
Individual patient-level data validation of surrogate and modified endpoints for immunotherapy in advanced hepatocellular carcinoma: Post-hoc analysis of IMbrave150 and real-world observations.
Authors: Mir Lim, Maishara Muquith, Bernadette Miramontes, Chieh-Ju Lee, Yi-Hsiang Huang, David Hsiehchen
Journal: Journal of Clinical Oncology (2023)

4090 Background: Immune checkpoint inhibitors (ICIs) have become the preferred treatment for advanced hepatocellular carcinoma (HCC). Surrogate endpoints including overall response rate (ORR) and progression-free survival (PFS) are preferred outcome measures in early-phase trials. However, ICIs can induce atypical patterns of response and progression, calling into question the validity of surrogate endpoints as predictive of overall survival (OS) benefit. We performed a post-hoc analysis of a large, randomized phase 3 clinical trial (IMbrave150) and cross-sectional analysis of a multi-institution real-world environment (RWE) to assess the OS surrogacy of ORR and PFS using Response Evaluation Criteria in Solid Tumors (RECIST), modified RECIST (mRECIST), or immune-modified RECIST (imRECIST) in patients treated with ICIs. Methods: The IMbrave150 cohort in our analysis included 279 out of 336 patients treated with atezolizumab and bevacizumab in the intent-to-treat population. The RWE cohort included 328 patients with Child-Pugh A or B disease treated in the first or subsequent-line setting with anti-PD-1/L1 therapies. RECIST, mRECIST, and imRECIST ORR and PFS data for the IMbrave150 cohort was determined by investigators and central review, while RECIST ORR and PFS data for the RWE cohort was determined by treating providers or retrospective review. Results: In the IMbrave150 and RWE cohorts, Child-Pugh A patients treated in the first-line setting with CR/PR showed greater OS versus patients with SD/PD (IMbrave150: HR 0.16, 95% CI 0.10-0.26; RWE: HR 0.25, 95% CI 0.15-0.43). CR was associated with the greatest OS benefit, followed by PR, SD, and PD. Patients treated in the second-line setting or with Child-Pugh B disease showed that ORR was able to discriminate OS benefit but hazard ratios were closer to the null. In both cohorts, there was a positive rank correlation between RECIST PFS and OS (IMbrave150: Kendall's τ = 0.44, p &lt; 0.001); RWE: Kendall's τ = 0.52, p &lt; 0.001). However, only 31-46% of the variance in OS rankings was explained by PFS rankings. mRECIST PFS and imRECIST PFS showed a positive rank correlation with OS, with an explained variance of 30% and 38% for mRECIST and imRECIST, respectively. Conclusions: Our results suggest that RECIST ORR is a robust surrogate endpoint in HCC treated with ICIs. In contrast, the explained variance between RECIST PFS and OS in both the IMbrave and RWE cohorts was limited. This may reflect the impact of ICIs on response to subsequent therapies which may extend OS benefit. Although prior studies have proposed that modifications to RECIST may lead to more accurate surrogate markers, mRECIST and imRECIST ORR or PFS in HCC treated with ICIs were not associated with greater predictive performance compared to RECIST.
Mutational and DNA fragment analysis may help in the triage of FIT+ patients enrolled in colorectal cancer screening programs.
Authors: Mauro Scimia, Francesco Pepe, Gianluca Russo, Umberto Malapelle, Hiromi Tanaka, Simone Scimia, Giancarlo Troncone, Maria Antonia Bianco
Journal: Journal of Clinical Oncology (2023)

e15546 * F. Pepe made an equal contribution Background: Mutational and DNA fragment analysis have already been investigated for a possible role in the detection of colorectal cancer. This pilot study, conducted at ASL NA 3 SUD (Naples, Italy) with the University of Naples Federico II, attempts to understand their possible role in the detection of Advanced Adenomas+ (AA+) and their potential ability to triage subjects with a positive FIT test for referral to colonoscopy. Methods: 160 FIT+ subjects of both genders, aged 50-74, participating in a colorectal cancer screening program were enrolled in a clinical trial focusing on a novel biomarker for colorectal cancer diagnostics. Of these, 14 subjects had disease (12 AAs and 2 colorectal cancers, from now on “CRC”). After ethical committee’s approval and release of informed consents, a 20 ml whole-blood sample was collected from each subject. Samples were centrifuged following standard procedures and stored at -80°C. DNA extraction was later performed using a Minielute kit (Qiagen). Mutational and DNA fragment analysis were performed using a qPCR-based technology: the ColoScape™ 2.5 kit (DiaCarta Inc, Pleasanton, CA). A logistic regression was run to determine the probability of disease in subjects showing positivity for predictors. Estimates of sensitivity, specificity, PPV, NPV (with 95% C.I.), PLR, NLR and Youden’s Index were also obtained. Results: The logistic regression showed statistical significance, with a p-value &lt; 0.0001, that is, the logistic regression model with provides a better fit than the model without the independent variable. ColoScape identified 12 subjects with disease out of 14, for a sensitivity of 86% (67%,100%); both CRCs were picked up by ColoScape together with 10 AAs. 2 AAs were missed. Out of 146 healthy subjects, 107 were successfully identified as negatives, for a specificity of 73% (66%, 80%). PPV was 24% (12%, 35%). NPV was 98% (96%, 100%). PLR, NLR and Youden’s Index were 3.21, 0.19 and 0.59 respectively. Conclusions: This pilot study was intended to provide performance indicators to design a larger population study that is currently underway. These preliminary findings suggest that liquid biopsy-based mutational and DNA fragment analysis can play a role in selecting subjects with a higher risk of returning a positive colonoscopy, thus potentially improving the quality of colorectal cancer screening programs and patients’ experience.
TROPION-Lung04: Phase 1b, multicenter study of datopotamab deruxtecan (Dato-DXd) in combination with immunotherapy ± carboplatin in advanced/metastatic non-small cell lung cancer (mNSCLC).
Authors: Hossein Borghaei, Saiama Naheed Waqar, Debora S. Bruno, Satoru Kitazono, Kazushige Wakuda, Alexander I. Spira, Jairo Olivares, Gabriel Mak, Susan Lovick, Louise Goodwin, Kyriakos P. Papadopoulos
Journal: Journal of Clinical Oncology (2023)

TPS3158 Background: Datopotamab deruxtecan (Dato-DXd) is a TROP2-directed antibody drug conjugate that has shown encouraging preliminary activity and safety in patients (pts) with lung or breast cancers. The TROPION-Lung04 study was designed to assess the safety, tolerability, and antitumor activity of Dato-DXd in combination with immunotherapy ± carboplatin in pts with advanced or metastatic NSCLC. Methods: TROPION-Lung04 (NCT04612751) is a Phase 1b, multicenter, open-label, 2-part, dose escalation/confirmation and expansion study in ≈232 pts without actionable genomic alterations. In Part 1 (dose escalation/confirmation), pts will be enrolled to 1 of up to 11 cohorts. Details of cohorts 1–4 (Dato-DXd [4 or 6 mg/kg] + durvalumab [1120 mg Q3W] ± up to 4 cycles of carboplatin [AUC 5] Q3W) were previously described (Borghaei H, et al. JTO 2021;16(10):S1098-S1099). Cohorts 5–11 were recently added to evaluate Dato-DXd in combination with bispecific immunotherapies AZD2936 (anti-PD-1/TIGIT) and MEDI5752 (anti-PD-1/CTLA-4) in treatment-naïve pts. Pts in cohorts 5–8 will receive Dato-DXd (4 or 6 mg/kg) + AZD2936 ± carboplatin; pts in cohorts 9–11 will receive Dato-DXd + MEDI5752 ± carboplatin. Cohorts 5 and 6 will recruit pts with PD-L1 tumor proportion score (TPS) ≥50% in Parts 1 and 2A, and PD-L1 TPS 1–49% in Part 2B. Cohorts 7–11 will recruit pts with PD-L1 TPS &lt; 50% only. Dose confirmation in Cohorts 5–11 will be guided by an mTPI-2 design where a minimum of 6 and a maximum of 9 pts will be assessed for dose-limiting toxicities (DLTs) during Cycle 1; if the DLT incidence meets prespecified toxicity criteria, Part 2 dose expansions may be opened. Pts may continue Dato-DXd or immunotherapy treatment until disease progression (per RECIST v1.1) or unacceptable toxicity. Study endpoints are shown in the table. Enrolment across all combination cohorts is ongoing. Clinical trial information: NCT04612751 . [Table: see text]
Identification of FEN1 as a prognostic marker and novel therapeutic target in gastric cancer harboring TP53 mutations.
Authors: Ting Deng
Journal: Journal of Clinical Oncology (2023)

e16057 Background: As a common tumor suppressor gene, TP53 gene mutation leads to persistent activation of multiple downstream effectors that drive the cancer phenotype. Approximately 50% of gastric cancer (GC) patients harbor TP53 mutations, which confer stronger tumor biology and shorter overall survival (OS). Given that TP53-mutated proteins have proven difficult to target directly, identifying genes that function closely with TP53 and targeting these genes appears to be a promising therapeutic strategy for TP53-mutated GC patients. Methods: TP53 functionally sensitive genes were identified by evaluating the correlation between gene-dependent scores from CRISPR knockout screens and TP53 mRNA expression in TP53 mutant GC cell lines in the Cancer Cell Line Encyclopedia (CCLE) database. If the correlation coefficient is ≥0.6, the gene was considered as TP53 functional sensitive gene. Then TP53 functionally sensitive genes associated with prognosis were screened out in The Cancer Genome Atlas (TCGA). PockDrug-Server was used to predict drug susceptibility of candidate genes. Results: The results showed that in 9 GC cell lines with TP53 mutations and 14 with TP53 wild-type, 4 genes (KLF5, FEN1, CCNA2, CCNB1) were identified as TP53 functional sensitive genes. Among the 4 genes, only FEN1 expression was significantly correlated with OS (HR=1.85, 95CI 1.06−3.26, P=0.029). Multivariate Cox regression analysis showed that high FEN1 expression was an independent predictor of prognosis in TP53-mutated GC. Pocket druggability prediction analysis presented that FEN1 had 8 drug-able pockets, four of which all have a druggability score of 0.8 or higher, including one pocket with a score of 1. Conclusions: These findings suggested that FEN1 was promising prognostic marker and therapeutic target in TP53-mutated GC.